PROJECT SUMMARY Background: Obesity and diabetes are important risk factors for morbidity and mortality in people with HIV (PWH), especially in sub-Saharan Africa where health systems are already grappling with a rapid rise in metabolic disease. Dolutegravir (DTG)-based antiretroviral therapy (ART) has recently been adopted as the first-line regimen in most of the region, despite evidence that it is associated with excess weight gain. While the HIV care system offers a capable health systems platform, obesity and diabetes prevention is not a current focus of care paradigms. Candidate: I am a Clinical Fellow in Infectious Diseases at Massachusetts General Hospital and a physician-scientist with doctoral-level training in global health epidemiology and a strong track record of published observational research. However, my recent experiences caring for PWH have led to a desire to gain new skills in the design and execution of interventional trials to prevent metabolic disease in this population. My overarching career goal is to become an independent, NIH-funded physician-scientist with expertise in the metabolic complications of treated HIV, and in developing and testing clinical interventions to prevent these complications. Training: To achieve research independence, I will require additional training in 1) obesity medicine and diabetes prevention, 2) behavioral model-based intervention design, and 3) the conduct and analysis of clinical trials to prevent metabolic complications of HIV. Mentors: My training and research plans will be overseen by my primary mentor Dr. Mark Siedner, who has extensive mentoring experience and conducts both observational cohort studies and clinical trials in South Africa. Drs. Janet Lo (obesity medicine and diabetes prevention), Christina Psaros (behavioral model-based intervention design), and Deborah Wexler (the conduct and analysis of clinical trials) will serve as co-mentors to provide additional focused expertise. I will also receive annual feedback from my Scientific Advisory Board, which includes Drs. Rochelle Walensky, Naomi Levitt, Robert Parker, and Till Brnighausen. Research: With guidance from my team of mentors, I will explore the metabolic effects of DTG among PWH in South Africa and develop and pilot an intervention to mitigate these complications through three specific aims: 1) To determine the behavioral correlates of weight change and glucose intolerance for PWH transitioning to DTG-based ART in South Africa; 2) To develop an acceptable and contextually appropriate intervention to prevent weight gain and diabetes in PWH on DTG-based ART in South Africa; and 3) To conduct a factorial-randomized feasibility study of interventions to prevent weight gain and diabetes among PWH on DTG-based ART versus usual care. We will carry out this research through existing collaborations with the Wellcome Trust-funded Africa Health Research Institute (AHRI). Through this period of training and research, I will be well positioned to achieve research independence and plan to submit an NIH R01 application in the fourth year of this project to test the efficacy of an intervention to prevent weight gain and diabetes in PWH in South Africa.